The stability of polypeptide and protein conformation in membranes is not well understood. Our knowledge from cytoplasmic proteins is inappropriate for this consideration. Electrostatic interactions and, in particular, hydrogen bonds play a much increased role among the forces that stabilize peptide conformations in membranes relative to cytoplasmic proteins. This is accomplished with both peptide - peptide and peptide - solvent interactions. The role of the solvent in these interactions is referred to here as the non-catalytic role. At the same time hydrogen bonds are critical for the interconversion of conformations by catalyzing the exchange of hydrogen bonds, hence a catalytic role for solvent. In this study we propose to demonstrate and characterize these roles for the solvent via studies of the pentadecapeptide, gramicidin A (gA) in both organic solvents and in lipid bilayers. gA has numerous stable conformations in organic solvents that will be studied in detail by solution NMR methods. In some organic solvents a variety of these conformations can be trapped, i.e. they don't interconvert and if they did the minimum energy conformer would be different from the one that is trapped. In other solvents that can donate hydrogen bonds the conformers readily interconvert. In lipid bilayers gA can exist in conformations other than the channel state, i.e. the lipid bilayer can also trap non- minimum energy conformations of a polypeptide. This has very significant implications for the regulation of protein and polypeptide activity in membranes. Is there, in fact, a mechanism for protein regulation that we as biochemists are not aware of? The catalytic role of solvent water and non-catalytic role of lipid will be characterized in light of structural rearrangements both in organic solvents (solution NMR) and in a lipid environment (solid state NMR). The prime goals are to learn more about the role of solvent in hydrophobic polypeptide conformation and conformational interconversion as well as the stability of polypeptides in membrane environments.